Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. May 15, 2017; 8(2): 67-76
Published online May 15, 2017. doi: 10.4291/wjgp.v8.i2.67
Combination curcumin and vitamin E treatment attenuates diet-induced steatosis in Hfe-/- mice
Mandy Heritage, Lesley Jaskowski, Kim Bridle, Catherine Campbell, David Briskey, Laurence Britton, Linda Fletcher, Luis Vitetta, V Nathan Subramaniam, Darrell Crawford
Mandy Heritage, Lesley Jaskowski, Kim Bridle, Laurence Britton, V Nathan Subramaniam, Darrell Crawford, School of Medicine, The University of Queensland, Brisbane 4120, Australia
Mandy Heritage, Lesley Jaskowski, Kim Bridle, Laurence Britton, Darrell Crawford, Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane 4120, Australia
Catherine Campbell, Envoi Specialist Pathologists, Brisbane 4120, Australia
David Briskey, School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane 4120, Australia
Linda Fletcher, Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane 4120, Australia
Luis Vitetta, The University of Sydney, Sydney Medical School, Sydney 2006, Australia
Luis Vitetta, Medlab Clinical Ltd, Sydney 2006, Australia
V Nathan Subramaniam, The QIMR Berghofer Medical Research Institute, Brisbane 4120, Australia
V Nathan Subramaniam, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4120, Australia
Author contributions: Heritage M, Jaskowski L and Briskey D performed all experiments for the study; Campbell C undertook histological scoring; Heritage M, Bridle K, Britton L, Fletcher L, Vitetta L, Subramaniam VN and Crawford D were responsible for study design, data analysis and manuscript editing; Heritage M and Bridle K wrote the manuscript; Subramaniam VN and Crawford D were the joint senior authors.
Institutional review board statement: No human subjects were used in this study.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethics Committees of QIMR Berghofer Medical Research Institute (P829) and the University of Queensland (313/11).
Conflict-of-interest statement: The authors report no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Kim Bridle, School of Medicine, The University of Queensland, Lower Lobby Level, Administration Building, Greenslopes Private Hospital, Newdegate Street, Brisbane 4120, Australia.
k.bridle@uq.edu.au
Telephone: +61-7-33460698 Fax: +61-7-38476236
Received: August 28, 2016
Peer-review started: September 1, 2016
First decision: October 31, 2016
Revised: December 1, 2016
Accepted: February 28, 2017
Article in press: March 2, 2017
Published online: May 15, 2017
Processing time: 260 Days and 16.5 Hours
AIM
To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe-/- high calorie diet model of steatohepatitis.
METHODS
Hfe-/- C57BL/6J mice were fed either a high calorie diet or a high calorie diet with 1 mg/g curcumin; 1.5 mg/g vitamin E; or combination of 1 mg/g curcumin + 1.5 mg/g vitamin E for 20 wk. Serum and liver tissue were collected at the completion of the experiment. Liver histology was graded by a pathologist for steatosis, inflammation and fibrosis. RNA and protein was extracted from liver tissue to examine gene and protein expression associated with fatty acid oxidation, mitochondrial biogenesis and oxidative stress pathways.
RESULTS
Hfe-/- mice fed the high calorie diet developed steatohepatitis and pericentral fibrosis. Combination treatment with curcumin and vitamin E resulted in a greater reduction of percent steatosis than either vitamin E or curcumin therapy alone. Serum alanine aminotransferase and non-alcoholic fatty liver disease (NAFLD) activity score were decreased following combination therapy with curcumin and vitamin E compared with high calorie diet alone. No changes were observed in inflammatory or fibrosis markers following treatment. Epididymal fat pad weights were significantly reduced following combination therapy, however total body weight and liver weight were unchanged. Combination therapy increased the mRNA expression of AdipoR2, Ppar-α, Cpt1a, Nrf-1 and Tfb2m suggesting enhanced fatty acid oxidation and mitochondrial biogenesis. In addition, combination treatment resulted in increased catalase activity in Hfe-/- mice.
CONCLUSION
Combination curcumin and vitamin E treatment decreases liver injury in this steatohepatitis model, indicating that combination therapy may be of value in NAFLD.
Core tip: The high prevalence of obesity and the metabolic syndrome suggests that many patients with liver disease of varying etiologies will have co-existent non-alcoholic fatty liver disease. Our model of co-toxic liver disease incorporates increased hepatic iron in combination with steatosis and was associated with necroinflammation and early hepatic fibrosis. Because of the beneficial effect of combination therapy, we believe vitamin E and curcumin should be investigated in other animal models of non-alcoholic steatohepatitis. Should beneficial effects be demonstrated, combination treatment with the development of appropriate dosing strategies could be rapidly moved to human studies allowing for an effective treatment strategy.
